Diagnosis of sensitivity and resistance against a specific anticancer agent is important for selecting the specific anticancer agent that is more effective for a specific patient with cancer. Therefore, biomarkers that can diagnose the sensitivity and the resistance against the specific anticancer agent have been actively explored. Examples of such an anticancer agent may include c-MET inhibitors and EGFR inhibitors.
(1) c-MET Inhibitor
It is shown that growth of a certain cancer can be inhibited by inhibiting c-MET (a receptor-type tyrosine kinase) that is one of oncogenes (Non-patent Literature 1), and development of a c-MET inhibitor as an anticancer agent has been advanced. There are many unclear points so far about the cancers that are sensitive against the c-MET inhibitor, which are effectively treated by the c-MET inhibitor, and the cancers caused by hyperactivation of a c-MET gene (e.g., cancers caused by amplification, mutation or the like of the c-MET gene) is promising candidates of the cancers that are sensitive against the c-MET inhibitor.
(2) EGFR Inhibitor
In cancer therapy with a molecular target drug such as an EGFR inhibitor (e.g., gefitinib), an event has become problematic in which a cancer that is effectively treated with the molecular target drug in early times lose its therapeutic effect during a long term treatment because of resistance against the molecular target drug. It is reported that the amplification of the c-MET gene is thought to be one of causes for this event (the amplification of the c-MET gene was confirmed in about 20% of patients with lung cancer which had acquired a resistance to gefitinib) (Non-patent Literature 2). It is also reported that the cancer in which the amplification of the c-MET gene is observed can be treated with simultaneous combination of the EGFR inhibitor and the c-MET inhibitor (Non-patent Literature 2).
Meanwhile, a method of measuring the amplification of the c-MET gene is available as a method capable of selecting the cancer that is sensitive against the c-MET inhibitor and the cancer that is resistant against the EGFR inhibitor. A FISH method capable of directly detecting the gene amplification is known as the method of measuring the amplification of the c-MET gene. However, the FISH method is problematic since it requires cumbersome steps that are treatments of cancer cells and detection of the gene amplification, and is difficult to be automated. Thus, it is expected to develop a method capable of diagnosing the sensitivity against the c-MET inhibitor and the resistance against the EGFR inhibitor conveniently.
Ectodomain shedding that is a phenomenon that a fragment of an extracellular domain of c-MET (a secretory form of c-MET) is released is reported for the c-MET gene (Patent Literature 1). It is also reported that the fragment of the extracellular domain of c-MET can be used as a biomarker for the cancer (Patent Literature 2) and the ectodomain shedding can be associated with malignancy of the cancer (Non-patent Literature 3).